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The suicide substrate reaction is a model for certain enzyme-inhibitingdrugs. This reaction system is examined assuming that the substratediffuses freely while the enzyme remains fixed. Two sets ofinitial and boundary conditions are examined: one modellingan instantaneous point source, akin to an injection of substrate,the other, a continuous point source, akin to a continuing influx,or intravenous drip, of substrate. The quasi-steady-state assumptionis applied to obtain analytical solutions for a limited parameterspace. Finally, further applications of numerical and analyticalexperimentation on pharmaceutical mechanisms are described. 相似文献
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JOHN P. BOURKE LYNNE HOWELL ALAN MURRAY WILLIAM E. HILL J. CAMPBELL COWAN KEVIN BEATT JOAN ERRINCTON STUART JAMESON RONALD G. GOLD 《Pacing and clinical electrophysiology : PACE》1989,12(8):1419-1425
A randomized prospective study was undertaken to compare the electrical performances of three permanent, endocardial, tined pacing leads with different electrode designs--sintered platinum, vitreous carbon, and porous carbon. Ninety-nine patients received one of the leads (S80 31; 423S 32; S100 36). Acute R wave amplitude and ST elevation of the native endocardial electrogram, voltage threshold, impedance, and current flow at four pulse durations (0.25-1.0 msec) were measured. Voltage thresholds were measured noninvasively at each of four pulse durations at 2 days and 1, 3, and 6 months after implantation. No significant differences were found in sensing properties, or current flow at threshold at 0.5 msec pulse duration. The 423S lead had a significantly higher impedance at threshold and both a higher impedance and lower current flow at 5 V. No significant differences in threshold voltages were found between the three leads at any pulse duration, at any of the assessed times after implantation. Six-month thresholds for the S80, 423S, and S100 leads were 1.18 +/- 0.35, 1.17 +/- 0.29, and 1.06 +/- 0.38 V respectively at 0.5 msec pulse duration. Differences between 'high performance' pacing leads need to be of a greater order of magnitude before they can be exploited to give any real clinical advantage to patients. 相似文献
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N. J. GOODERHAM S. MURRAY A. M. LYNCH R. J. EDWARDS M. YADOLLAHI-FARSANI C. BRATT K. J. RICH K. ZHAO B. P. MURRAY S. BHADRESA S. J. CROSBIE A. R. BOOBIS & D. S. DAVIES 《British journal of clinical pharmacology》1996,42(1):91-98
1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats. 相似文献
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats. 相似文献
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The best anastomotic agent to join nerve ends is controversial. This paper describes a controlled trial between a collagen tube wrap and a tissue glue to anastomose the rat facial nerve. There was no difference in the results using photographic, histological and electrophysiological techniques. 相似文献
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Pain following tonsillectomy is an important problem. It is caused by the surgical trauma of excision and haemostasis. Numerous surgical and pharmacological solutions have been tried, with disappointing results. Fibrin sealant is a widely used atraumatic haemostatic agent. This study aims to determine whether tonsillectomy with fibrin sealant haemostasis results in less post-operative pain than that with the conventional technique of diathermy. Fifty consecutive adult patients undergoing tonsillectomy were prospectively studied. They were randomized to receive either fibrin sealant or diathermy haemostasis. Other pain variables were controlled. Pain was measured by a visual linear analogue scale and inter-incisor distance on both the day of operation and the first post-operative day. The patients and pain measurer were blind to the randomization. The results showed that tonsillectomy with fibrin sealant haemostasis was significantly (P < 0.05) less painful than that with diathermy on both days studied and by both methods of pain measurement 相似文献
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